BACKGROUND: This study examined the relationship between serum glutathione peroxidase 1 (GPx-1) activity and endothelial dysfunction in the subjects with and without metabolic syndrome (MetS).METHODS: This case-control study was conducted on 76 subjects, 38 were patients with MetS and 38 were without MetS. The demographic, clinical, and laboratory features of the subjects were measured and then compared. The MetS was diagnosed according to the definitions of the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF). Serum GPx-1 activity was measured by standard methods. Endothelial dysfunction was assessed with flow-mediated dilation (FMD) technique.RESULTS: In case-control study of 76 subjects, all of MetS risk factors including abdominal obesity, triglyceride (TG), low serum level of high-density lipoprotein cholesterol (HDL-C), hypertension (HTN), and fasting plasma glucose (FPG) were significantly higher than healthy individuals (P < 0.050). FMD was significantly lower than normal subjects (P < 0.050). Serum GP-1 activity was significantly lower in patients with MetS compared to normal subjects (21.7 ± 13.5 vs. 79.0 ± 38.6, respectively) (P = 0.001). The value of GPx-1 was significantly correlated with diastolic blood pressure (DBP) (r = -0.249, P = 0.040), C-reactive protein (CRP) (r = -0.409, P = 0.014), and FMD (r = 0.293, P = 0.050) in patients with MetS. The results of logistic regression showed that a unite increase in CRP (mg/dl), FMD (%), and endothelin-1 (ET-1) (pg/ml) and a unit decrease in GPx significantly increased the odds ratio (OR) of MetS; after adjusting for age and sex the results remained significant except for FMD (P < 0.050)CONCLUSION: Endothelial dysfunction is related to serum GPx-1 activity in patients with MetS. GPX-1 activity is associated with risk of cardiovascular diseases (CVDs) and peripheral vascular diseases (PVDs) in patients with MetS.